title: Interleukin-3 plays dual roles in osteoclastogenesis by promoting the development of osteoclast progenitors but inhibiting the osteoclastogenic process.
abstract: Interleukin (IL)-3, a multilineage hematopoietic growth factor, is implicated in the regulation of osteoclastogenesis. However, the role of IL-3 in osteoclastogenesis remains controversial; whereas early studies showed that IL-3 stimulates osteoclastogenesis, recent investigations demonstrated that IL-3 inhibits osteoclast formation. The objective of this work is to further address the role of IL-3 in osteoclastogenesis. We found that IL-3 treatment of bone marrow cells generated a population of cells capable of differentiating into osteoclasts in tissue culture dishes in response to the stimulation of the monocyte/macrophage-colony stimulating factor (M-CSF) and the receptor activator of nuclear factor kappa B ligand (RANKL). The IL-3-dependent hematopoietic cells were able to further proliferate and differentiate in response to M-CSF stimulation and the resulting cells were also capable of forming osteoclasts with M-CSF and RANKL treatment. Interestingly, IL-3 inhibits M-CSF-/RANKL-induced differentiation of the IL-3-dependent hematopoietic cells into osteoclasts. The flow cytometry analysis indicates that while IL-3 treatment of bone marrow cells slightly affected the percentage of osteoclast precursors in the surviving populations, it considerably increased the percentage of osteoclast precursors in the populations after subsequent M-CSF treatment. Moreover, osteoclasts derived from IL-3-dependent hematopoietic cells were fully functional. Thus, we conclude that IL-3 plays dual roles in osteoclastogenesis by promoting the development of osteoclast progenitors but inhibiting the osteoclastogenic process. These findings provide a better understanding of the role of IL-3 in osteoclastogenesis.
authors.affiliation: Department of Hematology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, China; Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Huixian
authors.initials: H
authors.lastname: Hong
authors.forename: Zhenqi
authors.initials: Z
authors.lastname: Shi
authors.forename: Ping
authors.initials: P
authors.lastname: Qiao
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Erin M
authors.initials: EM
authors.lastname: McCoy
authors.forename: Ping
authors.initials: P
authors.lastname: Mao
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.forename: Xu
authors.initials: X
authors.lastname: Feng
authors.forename: Shunqing
authors.initials: S
authors.lastname: Wang
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D007377:Interleukin-3 / Q000494:pharmacology / Q000502:physiology*; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000166:cytology*
chemical_list: D007377:Interleukin-3; D016173:Macrophage Colony-Stimulating Factor
keywords: APC; BMC; BRC; CMP; Car2; Ctsk; FBS; GAPDH; GM-CSF; GMP; HSC; IL-3; IL-6; Interleukin-3; M-CSF; MMP9; MSC; Osteoclast precursor; Osteoclast progenitor; Osteoclastogenesis; PBS; PE; RANKL; RT-PCR; SCF; SEM; TRAP; allophycocyanin; bone marrow cells; bone remodeling compartment; carbonic anhydrase 2; cathepsin K; common myeloid progenitors; fetal bovine serum; glyceraldehyde 3-phosphate dehydrogenase; granulocyte/macrophage colony stimulating factor; granulocyte/macrophage progenitors; hematopoietic stem cells; interleukin 3; interleukin 6; matrix metalloproteinase 9; mesenchymal stem cells; monocyte/macrophage-colony stimulating factor; phosphate-buffered buffers; phycoerythrin; receptor activator of nuclear factor kappa B ligand; reverse transcription-polymerase chain reaction; scanning electron microscopy; stem cell factor; tartrate resistant acid phosphatase; α-MEM; α-minimal essential medium